The development of a successful vaccine against HIV infection or a vaccine agent capable of preventing HIV disease progression has been a public health goal for over 15 years. One of the immune responses that may be required to elicit a protective immune response against HIV infection is the generation of antibodies that are virus neutralizing.
The target of HIV-1 neutralizing antibodies (NA) is the envelope glycoprotein complex. This complex is a multimeric structure composed of three or four copies each of the gp120 surface and gp41 transmembrane glycoproteins (Luciw, 1996). There are a number of neutralization domains on each of the three or four heterodimeric components of the complex (Thali et al., 1992, 1993; Zwart et al., 1991; Moore et al., 1993; Trkola et al., 1996; Muster et al., 1993; Cotropia et al., 1996; Sabri et al., 1996). The amino acid compositions of the proteins vary substantially from strain to strain. Some of the neutralization domains are in regions which tend to vary greatly, while others are in regions which tend to be highly conserved. The variable neutralization domains include those in variable (V) regions 1, 2, and 3 of gp120, while the conserved domains include the primary receptor binding site, and other epitopes in gp120 and gp41. Amino acid sequence variation is undoubtedly the explanation for the variation that is seen in specificity of neutralization sensitivity among virus strains. However, it has not been possible to classify antigenic subtypes of HIV-1 based on genetic analyses, and various regions of the envelope complex even outside of the neutralization domains have been shown to contribute to antigenic variability (Thali et al., 1994; Back et al., 1993).
Recent findings indicate that the neutralization of primary isolates of HIV may be mediated primarily by antibodies directed against non-V3 region epitopes expressed on the oligomeric complex but not on monomeric gp120, while laboratory adapted strains are more readily neutralized by antibodies directed against V3 (Hioe et al., 1997; VanCott et al., 1997). The identity of the non-V3 epitopes recognized on primary isolates is not established. The presence of antibodies which have broadly neutralizing activity against primary isolates of many subtypes of HIV-1 in sera from infected people is unusual, but the nature of the envelope proteins in individuals with such antibodies may be of interest for defining the epitopes which may be broadly immunogenic in vaccines.